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A pH responsive complexation-based drug delivery system for oxaliplatin

A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is b...

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Detalles Bibliográficos
Autores principales: Li, Bin, Meng, Zhao, Li, Qianqian, Huang, Xiayang, Kang, Ziyao, Dong, Huajin, Chen, Junyi, Sun, Ji, Dong, Yansheng, Li, Jian, Jia, Xueshun, Sessler, Jonathan L., Meng, Qingbin, Li, Chunju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618340/
https://www.ncbi.nlm.nih.gov/pubmed/28970876
http://dx.doi.org/10.1039/c7sc01438d
Descripción
Sumario:A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is based on the direct host–guest encapsulation of OX by a pH-responsive receptor, carboxylatopillar[6]arene (CP6A). The binding affinities of CP6A for OX were found to be pH-sensitive at biologically relevant pH. For example, the association constant (K (a)) at pH 7.4 [K (a) = (1.02 ± 0.05) × 10(4) M(–1)] is 24 times larger than that at pH 5.4 [K (a) = (4.21 ± 0.06) × 10(2) M(–1)]. Encapsulation of OX within the CP6A cavity did not affect its in vitro cytotoxicity as inferred from comparison studies carried out in several cancer cells (e.g., the HepG-2, MCF-7, and A549 cell lines). On the other hand, complexation by CP6A serves to increase the inherent stability of OX in plasma by 2.8-fold over a 24 h incubation period. The formation of a CP6A⊃OX host–guest complex served to enhance in a statistically significant way the ability of OX to inhibit the regrowth of sarcoma 180 (S180) tumors in Kunming (KM) mice xenografts. The improved anticancer activity observed in vivo for CP6A⊃OX is attributed to the combined effects of enhanced stability of the host–guest complex and the pH-responsive release of OX. Specifically, it is proposed that OX is protected as the result of complex formation and then released effectively in the acidic tumor environment.